A Paper-Based Synthetic Biology Platform for the On-Demand Testing of Water Quality

用于水质按需检测的纸质合成生物学平台

• 批准号: 10483253
• 负责人: Khalid Kamal Alam
• 金额: $ 77.68万
• 依托单位: STEMLOOP, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483253
• 关键词: Address; Adoption; Aging; Americas; Analytical Chemistry; Area; Awareness; Biochemical; Biochemical Reaction; Biosensing Techniques; Biosensor; Cell-Free System; Cells; Characteristics; Chronic; Collection; Communities; Companions; Consumption; Contractor; Dangerousness; Detection; Development; Developmental Disabilities; Devices; Diagnostic Reagent Kits; Diagnostic Sensitivity; Engineering; Ensure; Environment; Event; Exposure to; Eye; Filtration; Flushing; Funding; Genetic; Goals; Gold; Health; Heavy Metals; Homologous Gene; Household; Inequality; Infrastructure; Instruction; Interview; Investments; Laboratories; Lateral; Lead; Lead levels; Life; Ligands; Logistics; Methods; Microfluidic Microchips; Molecular; Monitor; Outcome; Paper; Performance; Phase; Plumbing; Poison; Positioning Attribute; Procedures; Process; Production; Proteins; Public Health; Quality Control; Reaction; Reporter Genes; Running; Safety; Sampling; Schools; Sensitivity and Specificity; Series; Shipping; Signal Transduction; Site; Source; System; Technical Expertise; Techniques; Technology; Testing; Time; Toxin; Transportation; United States; Validation; Visual; Visualization; Water; Water Pollutants; Water Supply; Work; Zinc; aged; anthropogenesis; base; chronic Pb exposure; contaminated drinking water; cost; cross reactivity; design; drinking water; field study; hazard; home test; human centered design; improved; innovation; interest; lead contamination; lead exposure; manufacturing scale-up; microorganism; mobile application; operation; physically handicapped; preservation; prototype; quality assurance; remediation; response; risk mitigation; scale up; screening; sensor technology; success; synthetic biology; technology validation; tool; transcription factor; usability; validation studies; water quality; water sampling; water testing

PROJECT SUMMARY/ABSTRACT Safe drinking water is essential for public health yet is increasingly threatened by anthropogenic activities and aging infrastructure that contaminate it with heavy metals and other toxins. Most notable in the United States is the contamination of drinking water with lead, a heavy metal that is pervasive in America’s water infrastructure and indoor plumbing. Chronic exposure to lead results in numerous adverse health and societal outcomes and is an environmental injustice that widens inequalities. Upon discovery, lead contamination can be mitigated by changing drinking water source, flushing, and existing filtration technologies. However, as recent events such as the crises in Flint, MI or Newark, NJ exemplify, improper management can lead to major public health threats by creating community-wide exposure to dangerously high levels of lead. Lead contamination of drinking water is widespread across the United States due to aged infrastructure and domestic plumbing that heavily relied on lead. Frequent monitoring for the presence of lead contamination in drinking water is part of the solution. It can identify where problems exist, alert consumers without delay, and inform risk mitigation and remediation strategies. However, reliable testing remains limited to analytical chemistry techniques that are costly, time consuming, and require substantial laboratory infrastructure and technical expertise. This complicates the large- scale of testing needed to address the lead in drinking water crisis and is a barrier to the routine testing of water supplies by consumers. Here, we propose to address these issues by pursuing the next stage of development of our technology platform that will allow for the reliable, inexpensive, on-site, and on-demand monitoring of lead in drinking water. Our technology is built from recent innovations in synthetic biology that allow us to repurpose biological sensor proteins that detect specific toxic ligands, such as heavy metals, into ‘cell-free’ reactions that produce detectable signals when lead is present. These biochemical reactions are safe and can be embedded on paper devices for long term storage and distribution. Adding water to these paper-based devices activates the biochemical reaction and produces a visual signal in the presence of a toxic compound. This Phase II proposal details a series of complementary aims for achieving improved specificity and sensitivity of this lead testing device, using a human-centered design process to improve test operation and results interpretation, and adapting our manufacturing and quality assurance/quality control processes for a scale-up of manufacturing capability for validation studies. A successful outcome of this proposal will lead to a rapid lead test with sensitivity comparable to laboratory testing, an accessible and easy-to-use device format with a companion mobile app, and pilot-scale production to validate our lead sensing technology in the laboratory and in the field. This work will enable manufacturing and commercial distribution of a highly sensitive and rapid lead biosensor, which will help address the growing water quality crisis in the United States and beyond.

项目摘要/摘要 安全饮用水对于公共卫生至关重要，但越来越受人为活动的威胁和 老化的基础设施用重金属和其他毒素污染了它。在美国最著名的是 用铅污染饮用水，铅是一种在美国水基础设施中普遍存在的重金属 和室内管道。长期暴露于领导者中会导致许多不利的健康和社会成果以及 是环境不平等的不平等现象。发现后，可以通过 改变饮用水源，冲洗和现有的过滤技术。但是，作为最近的事件 由于弗林特，密歇根州或纽瓦克的危机，新泽西 通过创造社区范围内的危险较高铅的曝光。 lead 由于老化的基础设施和国内管道，全美都广泛地退休了 带领。频繁监测饮用水中存在铅污染的是该溶液的一部分。它可以 确定存在问题的位置，不延迟提醒消费者，并告知风险降低和补救 策略。但是，可靠的测试仍然仅限于分析化学技术，这些技术是昂贵的，时间 消费，需要大量的实验室基础设施和技术专业知识。这使大型 - 解决饮用水危机中的铅所需的测试规模，这是对水的常规测试的障碍 消费者的供应。在这里，我们建议通过追求下一阶段发展来解决这些问题 我们的技术平台将允许对铅的可靠，廉价，现场和点播监视 在饮用水中。我们的技术建立在合成生物学的最新创新中，使我们能够复制 检测特定有毒配体（例如重金属）的生物传感器蛋白，无细胞的反应 存在铅时产生的可检测信号。这些生化反应是 安全，可以嵌入 在纸设备上进行长期存储和分发。将水添加到这些纸基设备中激活 生化反应并在存在有毒化合物的情况下产生视觉信号。该阶段II 提案详细介绍了一系列补充目标，以提高该线索的特异性和敏感性 测试设备，使用以人为本的设计过程来改善测试操作和结果解释，并 调整我们的制造和质量保证/质量控制过程，以扩大制造业 该提案的成功结果将导致敏感性快速测试 可与实验室测试相媲美，这是一种可访问且易于使用的设备格式，具有伴侣移动应用程序， 和试点规模的生产以验证我们在实验室和现场中的铅传感技术。这项工作 将实现高度敏感和快速铅生物传感器的制造和商业分销，这将 帮助解决美国及以后的水质危机的日益增长。